Fibrin is an insoluble protein which is produced at the site of a wound through a chain reaction involving formation and activation of certain vascular proteins. A fibrous network of fibrin forms at the wound site and combines with blood platelets, thus producing a fibrin-platelet clot which stops the flow of blood from the wound. Fibrin-platelet clot formation is thus essential for the survival of humans and other animals. However, fibrin-platelet clot formation elsewhere in the body (i.e., at locations other than wound sites) causes a dangerous, potentially life-threatening restriction of blood flow. Blood clots, also known as thrombi, may remain at the original point of formation or may dislodge and travel through the bloodstream to a new site where the clot causes a sudden blocking of blood flow. Examples of the medical problems caused by abnormal fibrin-platelet clots include venous and arterial thromboses, heart attacks caused by thrombi in heart vessels, as well as pulmonary and cerebral thromboembolism. In addition, fibrin-platelet clots have been reported to occur at sites of infarcts and tumors, wherein fibrin may surround the damaged tissue or tumor, thus further aggravating the patient's condition. (See U.S. Pat. No. 4,418,052.) In view of the high incidence of medical problems associated with abnormal fibrin-platelet clots, much effort has been directed to development of techniques for diagnosing such conditions. Unfortunately, many of these techniques suffer from lack of specificity or reliability, while others require unacceptable lengths of time to complete the testing. Still other methods are designed to detect thrombi in the process of forming, but not preexisting clots.
Among the diagnostic methods which have been attempted is the use of radiolabeled proteins, such as enzymes, which either bind to or become incorporated within a clot, so that the clot can be imaged using techniques for detection of the radioisotope within the body. Such proteins include streptokinase, urokinase, tissue plasminogen activator, fibrokinase, streptokinase-activated human Plasmin, fibrin and certain fragments thereof. (See, for example,
U.S Pat. Nos. 4,427,646; 4,416,865; 4,418,052; and 4,663,146.) However, such problems as low specificity or affinity of the radiolabeled protein for a clot, denaturation of the protein during the radiolabeling procedures, and unstable attachment of the radioisotope to the protein have been associated with certain of these proposed diagnostic techniques. Thus, a need remains for an accurate, convenient method for early detection of abnormal fibrin-platelet clots within the body.